Pheromones stereochemistry

Stereochemistry and asymmetric synthesis are topics with which chemists traditionally have been concerned (1 ). In recent years there has been a virtual explosion of literature in the area of asymmetric organic synthesis that has fortuitously paralleled the increased awareness of insect pheromone stereochemistry. Many useful reviews of asymmetric synthesis exist (2, 2> 4, 5, 0 and this paper will only briefly direct the reader s attention to examples of reported syntheses by type that may be of potential general use for pheromone synthesis. It should be clear even to the casual reader that this field is in need of almost annual review and current literature would have to be consulted in the face of an original problem in synthesis. 

Synthesis, stereochemistry, and bioactivity of heterocyclic pheromones 97CC1153, 98CCC899, 98EJ01479. 

In 1952, it was reported that a constituent of excretions from female American cockroaches of the species Periplaneta ameri-cana is an extraordinarily potent sex pheromone.1 Early attempts to isolate and characterize the active compounds were hampered because individual cockroaches store only minute amounts of the pheromone ( 1 pg), and a full 25 years elapsed before Persoons et al. reported the isolation of two extremely active compounds, periplanones A and B.2 The latter substance is present in larger relative measure and its germacranoid structure (1, without stereochemistry) was tentatively assigned on the basis of spectroscopic data. Thus, in 1976, the constitution of periplanone B was known but there remained a stereochemical problem of a rather serious nature. Roughly three years intervened between the report of the gross structure of periplanone B and the first total synthesis of this substance by W. C. Still at Columbia.3... 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

There are three reviews emphasizing the importance of synthesis in pheromone science [4],in semiochemicals research [5],and in chemical ecology [6]. Stereochemistry-pheromone activity relationships are also discussed in the above three reviews, and more thoroughly in three other reviews [7-9]. 

By synthesizing pure enantiomers of pheromones, various stereochemistry-pheromone activity relationships could be clarified. For example, in the case of sulcatol (6-methyl-5-hepten-2-ol),both the enantiomers are necessary for bioactivity. For other relationships, please refer to [4-9]. 

Table 3 Stereochemistry of natural pheromones containing an epoxy ring (main components) and field attractancy of the synthetic racemate... 

Species Main pheromonal component Stereochemistry of the epoxy ring (main component) ... 

Some male arctiid moths produce their courtship pheromone from dietary pyrrolizidine alkaloids acquired during feeding by the larvae [ 126]. Conversion of monocrotaline to hydroxydanaidal by males is accomplished by aromatiza-tion, ester hydrolysis and oxidation of an alcohol to the aldehyde [7]. In the case of Utetheisa ornatirx the stereo-configuration at C7 of the dietary alkaloid is the same as the pheromone released (R). In contrast, another arctiid, Creatono-tos transiens, can convert a dietary precursor alkaloid with the (S) configuration at C7 (heliotrine) to (l )-hydroxydanaidal. The biosynthesis occurs by first oxidation-reduction at C7 to convert the stereochemistry and then proceeds through aromatization, hydrolysis, and oxidation [7]. 

Scheme 24 Unambiguous chiral synthesis of the (3S,4R)-enantiomer of the lactol pheromone of Biprorulus bibax to confirm the absolute stereochemistry [112]...

Syntheses of pheromones have been comprehensively treated by Mori [10-14]. The role of synthesis in the research on semiochemicals, the importance of stereochemistry in chemical signalling, and the significant relations between enantiomeric composition and biological activity of chiral semiochemicals have been thoroughly discussed by Mori [15-17]. In the present context, presentation of pheromone synthesis plays a minor role syntheses... 

Dimethylnonyl propanoate 196 (Scheme 22), the female produced sex pheromone of several corn root worm species, Diabrotica spp. keeps ( -configuration at the methyl branching, whereas the stereochemistry at the oxygen function may vary with species (including the formation of mixtures) [359,360]. The structure of the pheromone of the southern corn root worm D. undecim-punctata, ( )-10-methyltridecan-2-one 197, is closely related to 196 [361,362]. Compared with 196 and 197, (6R, 122 )-6,10-dimethylpentadecan-2-one 198, the sex pheromone of D. balteata shows similar structural features [363,364]. 

Removal of the auxiliary group from 12 (see p413) to give 13 followed by several steps yields (-)-(65)-tetrahydro-6-undecyl-2//-pyran-2-one (14), a pheromone of the wasp Vespa orientalis. Comparison of the optical rotation of the synthetic product with that of the natural product served to confirm the stereochemistry of the initial reduction to 12. 

As expected for the SAMP-alkylation, the (4S)-configuration was generated in excess. Thus, the absolute stereochemistry of (—)-serricornin (148) could be determined to be (4S,6S,7S). Other synthetic stereoisomers of serricornin prepared by Mori et al. 165) were almost devoid of pheromone activity. 

Hamilton, J. G. C Hooper, A. M., Ibbotson, H. C. el al. (1999b). 9-Methylgermacrene-B is confirmed as the sex pheromone of the sandfly Lutzomyia longipalpis from Lapinha, Brazil, and the absolute stereochemistry defined as S. Chemical Communications 2335-2336. 

Leal, W. S Shi, X., Liang, D., Schal, C. and Meinwald, J. (1995). Application of chiral gas chromatography with electroantennographic detection to the determination of the stereochemistry of a cockroach sex pheromone. Proceedings of the National Academy of Sciences, USA 92 1033-1037. 

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